Effluxing ABC transporters in human corneal epithelium

Kati Sisko Vellonen, Eliisa Mannermaa, Helen Turner, Marika Häkli, J. Mario Wolosin, Timo Tervo, Paavo Honkakoski, Arto Urtti

Research output: Contribution to journalArticlepeer-review

56 Scopus citations

Abstract

ATP-binding cassette (ABC) transporters are able to efflux their substrate drugs from the cells. Wecompared expression of efflux proteins in normal human corneal epithelial tissue, primary human corneal epithelial cells (HCEpiC), and corneal epithelial cell culture model (HCE model) based on human immortal cell line. Expression of multidrug resistance protein 1 (MDR1), multidrug resistance-associated protein 1-6 (MRP1-6) and breast cancer resistance protein (BCRP) was studied using quantitative RT-PCR, Western blot, and immunohistochemistry. Only MRP1, MRP5, and BCRP were expressed in the freshly excised human corneal epithelial tissue. Expression of MRP1 and MRP5 was localized predominantly in the basal cells of the central cornea and limbus. Functional efflux activity was shown in the cell models, but they showed overexpression of most efflux transporters compared to that of normal corneal epithelium. In conclusion, MRP1, MRP5, and BCRP are expressed in the corneal epithelium, but MDR1, MRP2, MRP3, MRP4, and MRP6 are not significantly expressed. HCE cell model and commercially available primary cells deviate from this expression profile.

Original languageEnglish
Pages (from-to)1087-1098
Number of pages12
JournalJournal of Pharmaceutical Sciences
Volume99
Issue number2
DOIs
StatePublished - Feb 2010

Keywords

  • ABC transporters
  • Cell culture
  • Cell model
  • Corneal epithelium
  • Efflux pumps
  • HCE
  • Multidrug resistance transporters
  • Multidrug resistance- associated proteins
  • P-glycoprotein
  • Primary cells

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